Febrile IllnessDEFINeNCT07004751
Etiology of Febrile Illness in Nepal (DEFINe Study)
A study testing Additional laboratory analysis in people with Febrile Illness and Fever Without Source, run by Patan Academy of Health Sciences at 1 site in Nepal.
Trial summary
In the absence of a microbiological lab testing, majority of the cases of febrile illnesses in Nepal are diagnosed on a clinical basis alone. These cases of "undifferentiated febrile illness" are treated empirically with multiple antibiotics without an etiological diagnosis. Read more about this study
- Who is it for?
- Ages 16 years and older
- Conditions the study is for
- Febrile Illness, Fever Without Source
- What is being tested?
- Additional laboratory analysis
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 194 participants
- Where
- 1 siteNepal
- Study dates
- 4 Jul 2025to 1 Oct 2026
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 16 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Age 16 years or older
- Documented fever (T ≥100.4F or ≥38C) of 3 days to 21 days duration
- No obvious diagnosis found on the basis of clinical, radiological, or initial routine laboratory tests*
- Admitted to the medical unit of hospital
- Signed ICF (informed consent form)
Who cannot join
- Outpatients
- Fever of less than 3 days or more than 21 days duration
- Patients being discharged from Emergency Room
- Children (younger than 16 years in age)**
- Immunocompromised patients
- Neutropenia (ANC <500 per cumm)
- Known case of HIV infection
- Admission to a hospital for 48-hours or longer within past 30 days
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Nepal1 site, 1 recruiting
- Recruiting
Patan Academy of Health Sciences
Lalitpur, Bagmati, 44709
Janak Koirala, MD MPH FIDSA, +9779818762117, janakkoirala@pahs.edu.np
Janak Koirala, MD MPH FIDSA
About this study
Official title: Determination of Etiology of Febrile Illness in Nepal (DEFINe Study)
In the absence of a microbiological lab testing, majority of the cases of febrile illnesses in Nepal are diagnosed on a clinical basis alone. These cases of "undifferentiated febrile illness" are treated empirically with multiple antibiotics without an etiological diagnosis. Unnecessary use of antibiotics can increase the risk of antibiotic resistance and adds unnecessary burden of cost to the patients and their families.
This study aims to determine the etiology of infections using additional microbiological techniques in patients admitted to the hospital with acute undifferentiated febrile illness of 3 days to 21 days duration, and assess its impact on use of antimicrobial drugs. In addition to the clinical features, the etiological diagnosis will be confirmed by using additional tests including culture techniques and ELISA based serological tests for 7 additional pathogens which are currently not tested in Nepal. Patients meeting definition of undifferentiated fever of 3 days to 21 days duration will be enrolled from a major tertiary care center using predefined inclusion and exclusion criteria.This study will help to identify additional infectious diseases prevalent in Nepal, decrease unnecessary empirical use of multiple antibiotics, and improve patient outcome. Additionally, identification of new causes of febrile illness will help in prevention and control of these infectious diseases at public health level.
Read the detailed description
Nepal is located between latitudes 26° and 31°N while its altitude ranges from 60m to 8848m from sea level allowing for a large variation in climate. Southern part of Nepal has tropical climate suitable for vector-borne tropical diseases whereas northern parts have more temperate and sub-arctic climate where these diseases are less common. Additionally, water-borne diseases have persisted because of a lack of sanitation and safe drinking water. Most hospitals in Nepal lack support of well equipped. microbiology laboratories for diagnosis of infectious diseases, and hence, most clinicians treat their patients empirically based on their decisions on clinical features alone . A study done in the region has shown poor predictability of clinical features alone to distinguish enteric fever from other causes of febrile illness .
Either from the lack of or limited access to confirmatory microbiological tests, majority of the cases of febrile illnesses in Nepal are diagnosed on clinical basis only. These cases of "undifferentiated fever" or "undifferentiated febrile illness" are treated empirically without etiological diagnosis. In the absence of correct diagnosis, patients receive multiple empirical antibiotics which increase the risk of antibiotic resistance and adds unnecessary burden of cost to the patients and their families. A hospital-based study of febrile patients published in 2004 revealed identifiable causes in only 37% of the patients.
The most common causes of febrile illness in Nepal at the time were enteric fever, murine typhus, scrub typhus, Leptospirosis, and bacterial infections including Streptococcus pneumoniae, Staphylococcus aureus, and Escherichia coli. Studies show a trend in increasing cases of rickettsial infections including Rickettsia typhi and Orientia tsutsugamushi.
Preliminary work done at Patan Hospital Patan Hospital is a tertiary care medical center with 450 beds that admits between 10 to 30 febrile patients per week depending on the season. Over 30% of these patients do not have localizing signs and symptoms for clinical diagnosis nor do they have a laboratory-based diagnosis. These cases are labelled as undifferentiated fever and receive empirical treatment with two or more antimicrobial agents. Previous studies done at Patan Hospital have demonstrated that Salmonella typhi and Salmonella paratyphi A were causes of undifferentiated fever of >3 days duration in 34% patients and Rickettsia typhi in 17% cases, whereas another study in 2008 found 7% cases of febrile illness has Rickettsia typhi, which is the cause of Murine typhus. These studies show an increase in cases of rickettsial infections including Riackettsia typhi and Orientia tsutsugamushi. Studies at Patan Hospital have also identified Streptococcus pneumoniae, Leptospira spp., Orientia tsutsugamushi, Hantavirus, and Coxiella burnetii as casues of febrile illnesses .
Research Gap The epidemiology of infectious disease has changed with massive within country urban migrations, increased migrant workers to India and overseas countries, change in climate, and several other reasons. Previous common causes of febrile illnesses such as malaria and enteric fever have declined over past decade whereas dengue and scrub typhus are on the rise. Meanwhile, new diseases such as COVID-19, dengue, and Scrub typhus have become commonplace [5,10,11]. Other causes of febrile illnesses, such as zoonoses (e.g. bartonellosis and Q fever), rickettsial (e.g. Q fever), and viral infections (e.g. arboviruses) remain mostly undiagnosed. This study aims to fill the gap in research by identifying additional causes and estimating burden of these infectious diseases. This will also help to reduce the unnecessary use of antibiotics.
- Conditions
- Febrile Illness, Fever Without Source
- Being tested
- Additional laboratory analysis, Standard of Care (SOC)
- Keywords
- Febrile Illnes
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Additional laboratory analysisDiagnostic test
Additional lab tests will be done to establish the diagnosis of Murine typhus, Bartonellosis, Q-fever, Chikungunya, Zika, Japanese B encephalitis, West Nile virus
Standard of Care (SOC)Diagnostic test
Standard of care evaluation of a febrile patient is done by the treating medical team as Standard of care evaluation of a febrile patient is done by the treating medical team which includes clinical, basic laboratory, radiological and microbiological evaluations
| Study group | Role | What they receive |
|---|---|---|
| Standard of Care | Active comparator | Standard of care evaluation of a febrile patient is done by the treating medical team which usually consists of the following set of clinical, basic laboratory, radiological and microbiological evaluations: History and Evaluation; Basic Lab Tests; Radiological Investigations; Routine Serologies; Microbiological Investigations Receives: Diagnostic Test: Standard of Care (SOC) |
| Study Arm | Experimental | For patients without an obvious cause of fever and an inconclusive work up after standard of care evaluations, additional serological tests as a part of undifferentiated febrile illness work up will be performed including clinical evaluation; additional microbiological evaluation and laboratory testing other than that in the standard care Receives: Diagnostic Test: Additional laboratory analysis |
What is being measured
The primary outcome is the main question the study is designed to answer.
Estimate the etiology of fever
To estimate the proportion of additional infectious etiologies of febrile illness among patients presenting with an undifferentiated fever of 3 to 21 days duration.
Measured: 0-21 days
Efficacy of antimicrobials
Average number of antimicrobials prescribed to participants diagnosed solely based on clinical diagnosis versus those with additional microbiological testing.
Measured: 0-21 days
Secondary outcomes (3)
appropriateness of the empiric antibiotic therapy
Percentage of participants receiving empiric antibiotic treatment with the final laboratory-confirmed diagnosis.
Measured: 0-21 days
correlation of clinical diagnosis with laboratory diagnosis
Percentage of cases where the initial clinical diagnosis matches the laboratory-confirmed diagnosis.
Measured: 0-21 days
Compare the Treatment outcome
Percentage of participants who gets clinical recovery by Day 21, comparing those treated based on microbiological diagnosis versus clinical diagnosis alone.
Measured: 0-21 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Jun 2025
- Study start4 Jul 2025
- Primary completion10 Jul 2026 (estimated)
- Study completion1 Oct 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Febrile IllnessStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- For patients without an obvious cause of fever and an inconclusive work up after standard of care evaluations, additional serological tests as a part of undifferentiated febrile illness work up will be performed including clinical evaluation; additional microbiological evaluation and laboratory testing
- Masking
- None (open label)
- Enrolment
- 194 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Patan Academy of Health Sciences
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Janak Koirala, Patan Academy of Health Sciences
- Investigators
- Janak Koirala, MD MPH, Principal investigator, Patan Academy of Health Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07004751
- Sponsor's protocol ID
- DEFINe Study
- Acronym
- DEFINe
- Status last verified
- Jul 2025
- First submitted
- 30 Apr 2025
- Last updated
- 3 Aug 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 3 Aug 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Determination of Etiology of Febrile Illness in Nepal (DEFINe Study)
- ClinicalTrials.gov ID
- NCT07004751
- Acronym / sponsor ID
- DEFINe / DEFINe Study
- Conditions
- Febrile Illness, Fever Without Source
- Keywords
- Febrile Illnes
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 194 participants (estimated)
- Lead sponsor
- Patan Academy of Health SciencesUniversity, hospital or other
- Study start
- 4 Jul 2025 (actual)
- Primary completion
- 10 Jul 2026 (estimated)
- Study completion
- 1 Oct 2026 (estimated)
- First posted
- 4 Jun 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
In the absence of a microbiological lab testing, majority of the cases of febrile illnesses in Nepal are diagnosed on a clinical basis alone. These cases of "undifferentiated febrile illness" are treated empirically with multiple antibiotics without an etiological diagnosis. Unnecessary use of antibiotics can increase the risk of antibiotic resistance and adds unnecessary burden of cost to the patients and their families.
This study aims to determine the etiology of infections using additional microbiological techniques in patients admitted to the hospital with acute undifferentiated febrile illness of 3 days to 21 days duration, and assess its impact on use of antimicrobial drugs. In addition to the clinical features, the etiological diagnosis will be confirmed by using additional tests including culture techniques and ELISA based serological tests for 7 additional pathogens which are currently not tested in Nepal. Patients meeting definition of undifferentiated fever of 3 days to 21 days duration will be enrolled from a major tertiary care center using predefined inclusion and exclusion criteria.This study will help to identify additional infectious diseases prevalent in Nepal, decrease unnecessary empirical use of multiple antibiotics, and improve patient outcome. Additionally, identification of new causes of febrile illness will help in prevention and control of these infectious diseases at public health level.
Detailed description
Nepal is located between latitudes 26° and 31°N while its altitude ranges from 60m to 8848m from sea level allowing for a large variation in climate. Southern part of Nepal has tropical climate suitable for vector-borne tropical diseases whereas northern parts have more temperate and sub-arctic climate where these diseases are less common. Additionally, water-borne diseases have persisted because of a lack of sanitation and safe drinking water. Most hospitals in Nepal lack support of well equipped. microbiology laboratories for diagnosis of infectious diseases, and hence, most clinicians treat their patients empirically based on their decisions on clinical features alone . A study done in the region has shown poor predictability of clinical features alone to distinguish enteric fever from other causes of febrile illness .
Either from the lack of or limited access to confirmatory microbiological tests, majority of the cases of febrile illnesses in Nepal are diagnosed on clinical basis only. These cases of "undifferentiated fever" or "undifferentiated febrile illness" are treated empirically without etiological diagnosis. In the absence of correct diagnosis, patients receive multiple empirical antibiotics which increase the risk of antibiotic resistance and adds unnecessary burden of cost to the patients and their families. A hospital-based study of febrile patients published in 2004 revealed identifiable causes in only 37% of the patients.
The most common causes of febrile illness in Nepal at the time were enteric fever, murine typhus, scrub typhus, Leptospirosis, and bacterial infections including Streptococcus pneumoniae, Staphylococcus aureus, and Escherichia coli. Studies show a trend in increasing cases of rickettsial infections including Rickettsia typhi and Orientia tsutsugamushi.
Preliminary work done at Patan Hospital Patan Hospital is a tertiary care medical center with 450 beds that admits between 10 to 30 febrile patients per week depending on the season. Over 30% of these patients do not have localizing signs and symptoms for clinical diagnosis nor do they have a laboratory-based diagnosis. These cases are labelled as undifferentiated fever and receive empirical treatment with two or more antimicrobial agents. Previous studies done at Patan Hospital have demonstrated that Salmonella typhi and Salmonella paratyphi A were causes of undifferentiated fever of >3 days duration in 34% patients and Rickettsia typhi in 17% cases, whereas another study in 2008 found 7% cases of febrile illness has Rickettsia typhi, which is the cause of Murine typhus. These studies show an increase in cases of rickettsial infections including Riackettsia typhi and Orientia tsutsugamushi. Studies at Patan Hospital have also identified Streptococcus pneumoniae, Leptospira spp., Orientia tsutsugamushi, Hantavirus, and Coxiella burnetii as casues of febrile illnesses .
Research Gap The epidemiology of infectious disease has changed with massive within country urban migrations, increased migrant workers to India and overseas countries, change in climate, and several other reasons. Previous common causes of febrile illnesses such as malaria and enteric fever have declined over past decade whereas dengue and scrub typhus are on the rise. Meanwhile, new diseases such as COVID-19, dengue, and Scrub typhus have become commonplace [5,10,11]. Other causes of febrile illnesses, such as zoonoses (e.g. bartonellosis and Q fever), rickettsial (e.g. Q fever), and viral infections (e.g. arboviruses) remain mostly undiagnosed. This study aims to fill the gap in research by identifying additional causes and estimating burden of these infectious diseases. This will also help to reduce the unnecessary use of antibiotics.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- For patients without an obvious cause of fever and an inconclusive work up after standard of care evaluations, additional serological tests as a part of undifferentiated febrile illness work up will be performed including clinical evaluation; additional microbiological evaluation and laboratory testing
| Arm | Type | Receives |
|---|---|---|
| Standard of Care | Active comparator | Diagnostic Test: Standard of Care (SOC)Standard of care evaluation of a febrile patient is done by the treating medical team which usually consists of the following set of clinical, basic laboratory, radiological and microbiological evaluations: History and Evaluation; Basic Lab Tests; Radiological Investigations; Routine Serologies; Microbiological Investigations |
| Study Arm | Experimental | Diagnostic Test: Additional laboratory analysisFor patients without an obvious cause of fever and an inconclusive work up after standard of care evaluations, additional serological tests as a part of undifferentiated febrile illness work up will be performed including clinical evaluation; additional microbiological evaluation and laboratory testing other than that in the standard care |
Who may qualify
- Ages
- 16 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (5 listed)
- Age 16 years or older
- Documented fever (T ≥100.4F or ≥38C) of 3 days to 21 days duration
- No obvious diagnosis found on the basis of clinical, radiological, or initial routine laboratory tests*
- Admitted to the medical unit of hospital
- Signed ICF (informed consent form)
Key exclusion criteria (8 listed)
- Outpatients
- Fever of less than 3 days or more than 21 days duration
- Patients being discharged from Emergency Room
- Children (younger than 16 years in age)**
- Immunocompromised patients
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Additional laboratory analysisAdditional lab tests will be done to establish the diagnosis of Murine typhus, Bartonellosis, Q-fever, Chikungunya, Zika, Japanese B encephalitis, West Nile virus | Diagnostic test | Study Arm |
| Standard of Care (SOC)Standard of care evaluation of a febrile patient is done by the treating medical team as Standard of care evaluation of a febrile patient is done by the treating medical team which includes clinical, basic laboratory, radiological and microbiological evaluations | Diagnostic test | Standard of Care |
Primary outcome
Estimate the etiology of fever
Time frame: 0-21 days
To estimate the proportion of additional infectious etiologies of febrile illness among patients presenting with an undifferentiated fever of 3 to 21 days duration.
Efficacy of antimicrobials
Time frame: 0-21 days
Average number of antimicrobials prescribed to participants diagnosed solely based on clinical diagnosis versus those with additional microbiological testing.
3 secondary outcomes
appropriateness of the empiric antibiotic therapy
Time frame: 0-21 days
correlation of clinical diagnosis with laboratory diagnosis
Time frame: 0-21 days
Compare the Treatment outcome
Time frame: 0-21 days
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Aug 2025.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Janak Koirala, MD MPH principal investigator
Patan Academy of Health Sciences
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Additional laboratory analysis in people with Febrile Illness and Fever Without Source, run by Patan Academy of Health Sciences at 1 site in Nepal.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 3 Aug 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Nepal. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Janak Koirala, MD MPH FIDSA (+9779818762117, janakkoirala@pahs.edu.np), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Estimate the etiology of fever (time frame: 0-21 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Aug 2025.